Ventricular tachycardia

Summary

Ventricular tachycardia (MONDO:0005477) is a disease with 34 cohort genes and 283 clinical trials. The dominant Reactome pathway is Muscle contraction (10 cohort genes). Top therapeutic interventions include amiodarone, alcohol, and dantrolene.

At a glance

• Cohort genes: 34
• ClinVar variants: 76
• Clinical trials: 283

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ventricular tachycardia
Mondo ID	MONDO:0005477
EFO	EFO:0005306
MeSH	D017180
ICD-10-CM	I47.2
ICD-11	1171837620
NCIT	C50802
SNOMED CT	25569003
UMLS	C0042514
MedGen	12068
Is cancer (heuristic)	no

Data availability: 76 ClinVar variants · 3 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › cardiac rhythm disease › ventricular tachycardia

Related subtypes (16): ventricular fibrillation, cardiac arrest, atrial fibrillation, atrial tachycardia, torsade-de-pointes syndrome with short coupling interval, sinoatrial node dysfunction and deafness, sino-auricular heart block, multifocal atrial tachycardia, His bundle tachycardia, incessant infant ventricular tachycardia, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, sudden arrhythmia death syndrome, cardiac conduction defect, sudden cardiac arrest, cardiac conduction disease with or without cardiomyoopathy, cardiogenetic rhythm disorder

Subtypes (3): torsades de pointes, ventricular tachycardia, familial, polymorphic ventricular tachycardia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

76 retrieved; paginated sample, class counts are floors:

36 conflicting classifications of pathogenicity, 18 uncertain significance, 8 benign/likely benign, 4 likely benign, 4 likely pathogenic, 2 pathogenic/likely pathogenic, 2 not provided, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
143947	NM_004415.4(DSP):c.2131_2132del	DSP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67568	NM_000891.3(KCNJ2):c.244C>T (p.Arg82Trp)	KCNJ2	Pathogenic	criteria provided, multiple submitters, no conflicts
177995	NM_001005242.3(PKP2):c.2377del (p.Ser793fs)	PKP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
45075	NM_001005242.3(PKP2):c.269_272del (p.Leu90fs)	PKP2	Likely pathogenic	no assertion criteria provided
691660	NM_002834.5(PTPN11):c.854-1G>C	PTPN11	Likely pathogenic	criteria provided, single submitter
691705	NM_000335.5(SCN5A):c.4296+1dup	SCN5A	Likely pathogenic	criteria provided, single submitter
2578378	NM_001267550.2(TTN):c.50723del (p.Lys16908fs)	TTN-AS1	Likely pathogenic	criteria provided, single submitter
35627	NM_020297.4(ABCC9):c.2200G>A (p.Val734Ile)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347347	NM_001148.6(ANK2):c.11300A>T (p.Glu3767Val)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
392350	NM_000719.7(CACNA1C):c.1555G>A (p.Ala519Thr)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
456964	NM_000719.7(CACNA1C):c.3391G>A (p.Asp1131Asn)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180286	NM_000719.7(CACNA1C):c.5599C>T (p.Arg1867Trp)	CACNA1C-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161212	NM_201596.3(CACNB2):c.1511C>T (p.Thr504Ile)	CACNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228635	NM_004415.4(DSP):c.1483G>A (p.Val495Met)	DSP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
373738	NM_004415.4(DSP):c.479G>A (p.Arg160Gln)	DSP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
405228	NM_004415.4(DSP):c.4565C>T (p.Thr1522Met)	DSP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523441	NM_001386795.1(DTNA):c.68-7G>A	DTNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355443	NM_004100.5(EYA4):c.347C>T (p.Ala116Val)	EYA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
36137	NM_001079802.2(FKTN):c.1297A>G (p.Thr433Ala)	FKTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
200964	NM_170707.4(LMNA):c.647G>A (p.Arg216His)	LMNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
137799	NM_001267550.2(TTN):c.59344+3G>A	LOC126806424	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14151	NM_002471.4(MYH6):c.3010G>T (p.Ala1004Ser)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
237434	NM_000257.4(MYH7):c.2581G>A (p.Glu861Lys)	MYH7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
46526	NM_033118.4(MYLK2):c.4G>A (p.Ala2Thr)	MYLK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180471	NM_001005242.3(PKP2):c.176A>T (p.Gln59Leu)	PKP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
222764	NM_001005242.3(PKP2):c.980G>T (p.Gly327Val)	PKP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
36681	NM_001005242.3(PKP2):c.1627G>A (p.Val543Ile)	PKP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201374	NM_001035.3(RYR2):c.1454G>A (p.Arg485Gln)	RYR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
36767	NM_000335.5(SCN5A):c.647C>T (p.Ser216Leu)	SCN5A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
48295	NM_000335.5(SCN5A):c.2770G>A (p.Val924Ile)	SCN5A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 131 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RYR2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
RYR2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
RYR2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
RYR2	Orphanet:3286	Catecholaminergic polymorphic ventricular tachycardia
SCN5A	Orphanet:101016	Romano-Ward syndrome
SCN5A	Orphanet:130	Brugada syndrome
SCN5A	Orphanet:1344	Isolated atrial standstill
SCN5A	Orphanet:154	Familial isolated dilated cardiomyopathy
SCN5A	Orphanet:166282	Hereditary sick sinus syndrome
SCN5A	Orphanet:228140	Idiopathic ventricular fibrillation
SCN5A	Orphanet:334	Hereditary atrial fibrillation
SCN5A	Orphanet:871	Hereditary progressive cardiac conduction defect
SNTA1	Orphanet:101016	Romano-Ward syndrome
SOS1	Orphanet:2024	Hereditary gingival fibromatosis
SOS1	Orphanet:648	Noonan syndrome
TCAP	Orphanet:154	Familial isolated dilated cardiomyopathy
TCAP	Orphanet:34514	Telethonin-related limb-girdle muscular dystrophy R7
TTN	Orphanet:140922	Titin-related limb-girdle muscular dystrophy R10
TTN	Orphanet:154	Familial isolated dilated cardiomyopathy
TTN	Orphanet:169186	Autosomal recessive centronuclear myopathy
TTN	Orphanet:178464	Hereditary myopathy with early respiratory failure
TTN	Orphanet:289377	Early-onset myopathy with fatal cardiomyopathy
TTN	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
TTN	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
TTN	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
TTN	Orphanet:324604	Classic multiminicore myopathy
TTN	Orphanet:334	Hereditary atrial fibrillation
TTN	Orphanet:466921	Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome
TTN	Orphanet:609	Tibial muscular dystrophy
TTN	Orphanet:707983	Early-onset autosomal recessive TTN-related distal myopathy
VCL	Orphanet:154	Familial isolated dilated cardiomyopathy
CACNA1C	Orphanet:101016	Romano-Ward syndrome
CACNA1C	Orphanet:130	Brugada syndrome
CACNA1C	Orphanet:528084	Non-specific syndromic intellectual disability
CACNA1C	Orphanet:595098	Timothy syndrome type 1
CACNA1C	Orphanet:595105	Timothy syndrome type 2
CACNA1C	Orphanet:595109	Atypical Timothy syndrome
CACNB2	Orphanet:130	Brugada syndrome
LDB3	Orphanet:154	Familial isolated dilated cardiomyopathy
LDB3	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
LDB3	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
LDB3	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
LDB3	Orphanet:54260	Left ventricular noncompaction
LDB3	Orphanet:98912	Late-onset distal myopathy, Markesbery-Griggs type
HCN4	Orphanet:130	Brugada syndrome
HCN4	Orphanet:166282	Hereditary sick sinus syndrome
TRPM4	Orphanet:130	Brugada syndrome
TRPM4	Orphanet:316	Progressive symmetric erythrokeratodermia
TRPM4	Orphanet:871	Hereditary progressive cardiac conduction defect
RBM20	Orphanet:154	Familial isolated dilated cardiomyopathy

Cohort genes → proteins

34 cohort genes, 32 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	34

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RYR2	HGNC:10484	ENSG00000198626	Q92736	Ryanodine receptor 2	clinvar
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	clinvar
SNTA1	HGNC:11167	ENSG00000101400	Q13424	Alpha-1-syntrophin	clinvar
SOS1	HGNC:11187	ENSG00000115904	Q07889	Son of sevenless homolog 1	clinvar
TCAP	HGNC:11610	ENSG00000173991	O15273	Telethonin	clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
VCL	HGNC:12665	ENSG00000035403	P18206	Vinculin	clinvar
CACNA1C	HGNC:1390	ENSG00000151067	Q13936	Voltage-dependent L-type calcium channel subunit alpha-1C	clinvar
CACNB2	HGNC:1402	ENSG00000165995	Q08289	Voltage-dependent L-type calcium channel subunit beta-2	clinvar
LDB3	HGNC:15710	ENSG00000122367	O75112	LIM domain-binding protein 3	clinvar
MYLK2	HGNC:16243	ENSG00000101306	Q9H1R3	Myosin light chain kinase 2, skeletal/cardiac muscle	clinvar
HCN4	HGNC:16882	ENSG00000138622	Q9Y3Q4	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4	clinvar
TRPM4	HGNC:17993	ENSG00000130529	Q8TD43	Transient receptor potential cation channel subfamily M member 4	clinvar
RBM20	HGNC:27424	ENSG00000203867	Q5T481	RNA-binding protein 20	clinvar
DPP6	HGNC:3010	ENSG00000130226	P42658	A-type potassium channel modulatory protein DPP6	clinvar
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	clinvar
DTNA	HGNC:3057	ENSG00000134769	Q9Y4J8	Dystrobrevin alpha	clinvar
EYA4	HGNC:3522	ENSG00000112319	O95677	Protein phosphatase EYA4	clinvar
FKTN	HGNC:3622	ENSG00000106692	O75072	Ribitol-5-phosphate transferase FKTN	clinvar
AKAP9	HGNC:379	ENSG00000127914	Q99996	A-kinase anchor protein 9	clinvar
TTN-AS1	HGNC:44124	ENSG00000237298		TTN antisense RNA 1	clinvar
ANK2	HGNC:493	ENSG00000145362	Q01484	Ankyrin-2	clinvar
ITFG2-AS1	HGNC:53128	ENSG00000258325		ITFG2 antisense RNA 1	clinvar
ABCC9	HGNC:60	ENSG00000069431	O60706	ATP-binding cassette sub-family C member 9	clinvar
KCNH2	HGNC:6251	ENSG00000055118	Q12809	Voltage-gated inwardly rectifying potassium channel KCNH2	clinvar
KCNJ2	HGNC:6263	ENSG00000123700	P63252	Inward rectifier potassium channel 2	clinvar
LAMA4	HGNC:6484	ENSG00000112769	Q16363	Laminin subunit alpha-4	clinvar
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	clinvar
MYH6	HGNC:7576	ENSG00000197616	P13533	Myosin-6	clinvar
MYH7	HGNC:7577	ENSG00000092054	P12883	Myosin-7	clinvar
PKP2	HGNC:9024	ENSG00000057294	Q99959	Plakophilin-2	clinvar
PRKAG2	HGNC:9386	ENSG00000106617	Q9UGJ0	5’-AMP-activated protein kinase subunit gamma-2	clinvar
PTPN11	HGNC:9644	ENSG00000179295	Q06124	Tyrosine-protein phosphatase non-receptor type 11	clinvar
RAF1	HGNC:9829	ENSG00000132155	P04049	RAF proto-oncogene serine/threonine-protein kinase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RYR2	Ryanodine receptor 2	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction.
SCN5A	Sodium channel protein type 5 subunit alpha	Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SNTA1	Alpha-1-syntrophin	Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins.
SOS1	Son of sevenless homolog 1	Promotes the exchange of Ras-bound GDP by GTP.
TCAP	Telethonin	Muscle assembly regulating factor.
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
VCL	Vinculin	Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion.
CACNA1C	Voltage-dependent L-type calcium channel subunit alpha-1C	Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.
CACNB2	Voltage-dependent L-type calcium channel subunit beta-2	Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current.
LDB3	LIM domain-binding protein 3	May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton.
MYLK2	Myosin light chain kinase 2, skeletal/cardiac muscle	Implicated in the level of global muscle contraction and cardiac function.
HCN4	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4	Hyperpolarization-activated ion channel that are permeable to Na(+) and K(+) ions with very slow activation and inactivation.
TRPM4	Transient receptor potential cation channel subfamily M member 4	Calcium-activated selective cation channel that mediates membrane depolarization.
RBM20	RNA-binding protein 20	RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes encoding key structural proteins involved in cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH.
DPP6	A-type potassium channel modulatory protein DPP6	Promotes cell surface expression of the potassium channel KCND2.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
DTNA	Dystrobrevin alpha	May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors.
EYA4	Protein phosphatase EYA4	Tyrosine phosphatase that specifically dephosphorylates ‘Tyr-142’ of histone H2AX (H2AXY142ph). ‘Tyr-142’ phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair…
FKTN	Ribitol-5-phosphate transferase FKTN	Catalyzes the transfer of a ribitol-phosphate from CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydra…
AKAP9	A-kinase anchor protein 9	Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus.
ANK2	Ankyrin-2	Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells.
ABCC9	ATP-binding cassette sub-family C member 9	Subunit of ATP-sensitive potassium channels (KATP).
KCNH2	Voltage-gated inwardly rectifying potassium channel KCNH2	Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel.
KCNJ2	Inward rectifier potassium channel 2	Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.
LAMA4	Laminin subunit alpha-4	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
LMNA	Prelamin-A/C	Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane.
MYH6	Myosin-6	Muscle contraction.
MYH7	Myosin-7	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.
PKP2	Plakophilin-2	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
PRKAG2	5’-AMP-activated protein kinase subunit gamma-2	AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism.
PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.
RAF1	RAF proto-oncogene serine/threonine-protein kinase	Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including prolifer…

Protein-family classification

Druggable: 13 · Difficult: 10 · Unknown: 11 · Druggable fraction: 0.38

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	7	23.0×	1e-07
Scaffold/PPI	7	3.6×	0.012
Kinase	3	2.5×	0.328
Phosphatase	1	2.5×	0.570
Transporter	1	2.3×	0.570
Protease	1	1.1×	0.814
Transcription factor	3	0.7×	0.911
Other/Unknown	11	0.6×	0.998

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RYR2	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom
SCN5A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a5su
SNTA1	Scaffold/PPI	no		PDZ, PH_domain, PH-like_dom_sf
SOS1	Scaffold/PPI	no		DH_dom, Ras-like_Gua-exchang_fac_N, PH_domain
TCAP	Other/Unknown	no		Telethonin, Titin-like_dom_sf
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
VCL	Other/Unknown	no		Vinculin_CS, Vinculin/catenin, Vinculin
CACNA1C	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
CACNB2	Scaffold/PPI	no		VDCC_L_bsu, SH3_domain, VDCC_L_b2su
LDB3	Transcription factor	no		PDZ, Znf_LIM, Zasp-like_motif
MYLK2	Kinase	yes	2.7.11.18	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
HCN4	Ion channel	yes		cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG, Ion_trans_dom
TRPM4	Ion channel	yes		Ion_trans_dom, TRPM_SLOG, TRPM
RBM20	Transcription factor	no		RRM_dom, Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2
DPP6	Protease	yes		Peptidase_S9_cat, Peptidase_S9B_N, AB_hydrolase_fold
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin
DTNA	Transcription factor	no		Znf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1
EYA4	Other/Unknown	no		EYA_dom, EYA, EYA_dom_sf
FKTN	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, FKTN/MNN-like, FKTN_N
AKAP9	Other/Unknown	no		ELK_dom, PACT_domain, AKAP9/Pericentrin
TTN-AS1	Other/Unknown	no
ANK2	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt
ITFG2-AS1	Other/Unknown	no
ABCC9	Transporter	yes		ABCC8/9, ABCC9, ABC_transporter-like_ATP-bd
KCNH2	Ion channel	yes		PAS, cNMP-bd_dom, PAS-assoc_C
KCNJ2	Ion channel	yes		K_chnl_inward-rec_Kir2.1, K_chnl_inward-rec_Kir_cyto, K_chnl_inward-rec_Kir_N
LAMA4	Other/Unknown	no		EGF, Laminin_G, LE_dom
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
MYH6	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
MYH7	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
PKP2	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold
PRKAG2	Other/Unknown	no		CBS_dom, CBS_dom_sf, AMPK_gamma/SDS23_families
PTPN11	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, SH2
RAF1	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE

Expression context

Cohort genes with no expression data: 0.

28 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	34
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	9
hindlimb stylopod muscle	7
gastrocnemius	5
skeletal muscle tissue of biceps brachii	4
cardiac atrium	4
right atrium auricular region	4
left ventricle myocardium	3
skeletal muscle tissue of rectus abdominis	3
cardiac muscle of right atrium	3
heart right ventricle	2
myocardium	2
jejunal mucosa	2
biceps brachii	2
adrenal tissue	2
mucosa of stomach	2
globus pallidus	2
medial globus pallidus	2
muscle of leg	2
dorsal motor nucleus of vagus nerve	2
cardiac ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RYR2	210	broad	marker	heart right ventricle, left ventricle myocardium, myocardium
SCN5A	161	broad	yes	apex of heart, heart left ventricle, cardiac ventricle
SNTA1	266	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
SOS1	289	ubiquitous	marker	colonic epithelium, jejunal mucosa, tendon of biceps brachii
TCAP	213	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
VCL	300	ubiquitous	marker	saphenous vein, blood vessel layer, urethra
CACNA1C	134	broad	marker	apex of heart, right coronary artery, muscle layer of sigmoid colon
CACNB2	237	broad	marker	adrenal tissue, mucosa of stomach, buccal mucosa cell
LDB3	247	broad	marker	skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle, apex of heart
MYLK2	148	tissue_specific	yes	hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis, gastrocnemius
HCN4	86	tissue_specific	yes	tibialis anterior, right atrium auricular region, cardiac atrium
TRPM4	201	ubiquitous	marker	mucosa of transverse colon, rectum, apex of heart
RBM20	191	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium
DPP6	221	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell
DSP	253	ubiquitous	marker	skin of hip, upper leg skin, hair follicle
DTNA	266	ubiquitous	marker	medial globus pallidus, globus pallidus, C1 segment of cervical spinal cord
EYA4	208	broad	marker	biceps brachii, skeletal muscle tissue of biceps brachii, seminal vesicle
FKTN	277	ubiquitous	yes	calcaneal tendon, adrenal tissue, germinal epithelium of ovary
AKAP9	292	ubiquitous	marker	jejunal mucosa, bronchial epithelial cell, cortical plate
TTN-AS1	174	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, right atrium auricular region
ANK2	281	ubiquitous	marker	substantia nigra pars compacta, lateral nuclear group of thalamus, substantia nigra pars reticulata
ITFG2-AS1	131	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, left testis
ABCC9	195	broad	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
KCNH2	211	broad	marker	apex of heart, right atrium auricular region, cardiac atrium
KCNJ2	256	ubiquitous	marker	inferior vagus X ganglion, skeletal muscle tissue of rectus abdominis, dorsal motor nucleus of vagus nerve
LAMA4	268	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, nerve
LMNA	295	ubiquitous	marker	nipple, mucosa of stomach, skin of abdomen
MYH6	154	tissue_specific	yes	cardiac muscle of right atrium, cardiac atrium, vena cava
MYH7	167	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 49.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNA	7,173
RAF1	6,574
ANK2	6,423
PTPN11	6,009
VCL	4,495
TTN	4,237
SOS1	3,625
AKAP9	3,537
PRKAG2	3,212
CACNA1C	3,145

Intra-cohort edges

A	B	Sources
ABCC9	EYA4	string_interaction
ABCC9	LDB3	string_interaction
ABCC9	RBM20	string_interaction
ABCC9	SCN5A	string_interaction
ABCC9	TCAP	string_interaction
AKAP9	KCNH2	string_interaction
AKAP9	SNTA1	string_interaction
ANK2	TTN	string_interaction
CACNA1C	CACNB2	intact, string_interaction
CACNA1C	HCN4	string_interaction
CACNA1C	KCNH2	string_interaction
CACNA1C	RYR2	biogrid_interaction, string_interaction
CACNB2	HCN4	string_interaction
CACNB2	KCNH2	string_interaction
CACNB2	SCN5A	string_interaction
DPP6	SCN5A	string_interaction
DSP	PKP2	string_interaction
DTNA	SNTA1	string_interaction
EYA4	FKTN	string_interaction
EYA4	PKP2	biogrid_interaction
EYA4	RBM20	string_interaction
EYA4	TCAP	string_interaction
FKTN	TCAP	string_interaction
HCN4	SCN5A	string_interaction
KCNH2	SCN5A	string_interaction
LDB3	MYH7	string_interaction
LDB3	RBM20	string_interaction
LDB3	TCAP	string_interaction
LDB3	TTN	string_interaction
LMNA	PKP2	string_interaction
MYH6	PRKAG2	intact
MYH6	TTN	string_interaction
MYH7	MYLK2	string_interaction
MYH7	PRKAG2	intact, string_interaction
MYH7	RBM20	string_interaction
MYH7	TCAP	string_interaction
MYH7	TTN	string_interaction
MYLK2	PRKAG2	string_interaction
PKP2	RYR2	string_interaction
PKP2	SCN5A	string_interaction
PTPN11	SOS1	biogrid_interaction, string_interaction
RAF1	SOS1	string_interaction
RBM20	SCN5A	string_interaction
RBM20	TCAP	string_interaction
RBM20	TTN	string_interaction
RYR2	SNTA1	intact
SCN5A	SNTA1	biogrid_interaction, string_interaction
SCN5A	TRPM4	string_interaction
TCAP	TTN	biogrid_interaction, intact, string_interaction

Structural data

PDB: 23 · AlphaFold-only: 9 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPN11	Q06124	115
SOS1	Q07889	91
RAF1	P04049	76
TTN	Q8WZ42	64
MYH7	P12883	43
VCL	P18206	37
CACNA1C	Q13936	33
TRPM4	Q8TD43	29
LMNA	P02545	28
RYR2	Q92736	26
KCNH2	Q12809	24
SCN5A	Q14524	16
ANK2	Q01484	11
HCN4	Q9Y3Q4	8
DPP6	P42658	8
DSP	P15924	4
CACNB2	Q08289	3
KCNJ2	P63252	3
TCAP	O15273	2
LDB3	O75112	2
MYLK2	Q9H1R3	2
DTNA	Q9Y4J8	1
PKP2	Q99959	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FKTN	O75072	92.48
ABCC9	O60706	81.72
SNTA1	Q13424	80.00
MYH6	P13533	74.91
LAMA4	Q16363	73.75
PRKAG2	Q9UGJ0	67.24
EYA4	O95677	63.79
RBM20	Q5T481	48.52
AKAP9	Q99996

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 319. Enrichment computed across 34 evidence-associated genes (27 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 27 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Muscle contraction	10	28.6×	2e-10	RYR2, SCN5A, TCAP, CACNA1C, CACNB2, AKAP9, ABCC9, KCNH2 (+2 more)
Cardiac conduction	8	32.2×	1e-08	RYR2, SCN5A, CACNA1C, CACNB2, AKAP9, ABCC9, KCNH2, KCNJ2
Phase 2 - plateau phase	3	84.6×	6e-04	CACNA1C, CACNB2, AKAP9
Signaling by BRAF and RAF1 fusions	4	25.2×	0.001	VCL, AKAP9, LMNA, RAF1
Phase 0 - rapid depolarisation	3	38.5×	0.004	SCN5A, CACNA1C, CACNB2
Striated Muscle Contraction	3	34.3×	0.004	TCAP, TTN, MYH6
Formation of the dystrophin-glycoprotein complex (DGC)	3	34.3×	0.004	SNTA1, DTNA, LAMA4
NCAM signaling for neurite out-growth	3	30.2×	0.005	SOS1, CACNA1C, CACNB2
Phase 3 - rapid repolarisation	2	84.6×	0.008	AKAP9, KCNH2
Activated NTRK2 signals through FRS2 and FRS3	2	70.5×	0.009	SOS1, PTPN11
Axon guidance	5	8.4×	0.009	SCN5A, SOS1, CACNA1C, CACNB2, ANK2
Neuronal System	5	8.2×	0.009	CACNB2, ABCC9, KCNH2, KCNJ2, PRKAG2
Nervous system development	5	8.0×	0.009	SCN5A, SOS1, CACNA1C, CACNB2, ANK2
Integration of energy metabolism	3	19.5×	0.011	CACNA1C, CACNB2, PRKAG2
Signaling by FLT3 ITD and TKD mutants	2	56.4×	0.012	SOS1, PTPN11
Inwardly rectifying K+ channels	2	52.9×	0.013	ABCC9, KCNJ2
Tie2 Signaling	2	44.5×	0.017	SOS1, PTPN11
Potassium Channels	3	14.9×	0.018	ABCC9, KCNH2, KCNJ2
FRS-mediated FGFR3 signaling	2	40.3×	0.018	SOS1, PTPN11
FRS-mediated FGFR4 signaling	2	36.8×	0.021	SOS1, PTPN11
FRS-mediated FGFR1 signaling	2	33.8×	0.024	SOS1, PTPN11
FRS-mediated FGFR2 signaling	2	32.5×	0.024	SOS1, PTPN11
Adrenaline,noradrenaline inhibits insulin secretion	2	29.2×	0.029	CACNA1C, CACNB2
Downstream signal transduction	2	28.2×	0.030	SOS1, PTPN11
Interaction between L1 and Ankyrins	2	27.3×	0.031	SCN5A, ANK2
FLT3 Signaling	2	25.6×	0.032	SOS1, PTPN11
Signaling by CSF1 (M-CSF) in myeloid cells	2	25.6×	0.032	SOS1, PTPN11
Interleukin-3, Interleukin-5 and GM-CSF signaling	2	23.5×	0.034	SOS1, PTPN11
Signaling by high-kinase activity BRAF mutants	2	23.5×	0.034	VCL, RAF1
Signaling by MET	2	23.5×	0.034	SOS1, LAMA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 32 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of heart rate by cardiac conduction	11	128.7×	7e-19	SCN5A, CACNA1C, CACNB2, HCN4, TRPM4, DSP, AKAP9, ANK2 (+3 more)
cardiac muscle contraction	8	100.3×	2e-12	RYR2, SCN5A, TCAP, TTN, MYLK2, KCNH2, MYH6, MYH7
ventricular cardiac muscle cell action potential	6	185.9×	4e-11	RYR2, SCN5A, SNTA1, ANK2, KCNH2, PKP2
regulation of heart rate	7	102.4×	4e-11	RYR2, SCN5A, SNTA1, HCN4, ANK2, MYH6, MYH7
striated muscle contraction	6	158.0×	9e-11	RYR2, TTN, MYLK2, DTNA, MYH6, MYH7
regulation of ventricular cardiac muscle cell action potential	5	219.4×	1e-09	RYR2, CACNA1C, TRPM4, DSP, PKP2
membrane depolarization during AV node cell action potential	4	421.3×	3e-09	SCN5A, CACNA1C, CACNB2, TRPM4
regulation of ventricular cardiac muscle cell membrane repolarization	5	131.7×	1e-08	SCN5A, SNTA1, AKAP9, ANK2, KCNH2
membrane depolarization during cardiac muscle cell action potential	4	175.5×	3e-07	SCN5A, CACNA1C, HCN4, KCNJ2
membrane depolarization during atrial cardiac muscle cell action potential	3	526.6×	3e-07	SCN5A, CACNA1C, CACNB2
muscle filament sliding	4	131.7×	8e-07	TCAP, TTN, MYH6, MYH7
membrane depolarization during SA node cell action potential	3	316.0×	2e-06	SCN5A, HCN4, ANK2
SA node cell action potential	3	263.3×	4e-06	SCN5A, HCN4, ANK2
regulation of SA node cell action potential	3	263.3×	4e-06	RYR2, HCN4, ANK2
cardiac muscle cell action potential involved in contraction	4	87.8×	4e-06	SCN5A, CACNA1C, KCNJ2, PKP2
muscle contraction	5	32.5×	1e-05	SNTA1, TTN, HCN4, MYH6, MYH7
cardiac muscle hypertrophy	3	158.0×	2e-05	RYR2, TCAP, TTN
cardiac muscle tissue morphogenesis	3	131.7×	3e-05	TCAP, TTN, MYLK2
cell communication by electrical coupling involved in cardiac conduction	3	131.7×	3e-05	RYR2, CACNA1C, PKP2
sarcomere organization	4	47.9×	3e-05	TCAP, TTN, LDB3, MYH6
potassium ion import across plasma membrane	4	45.8×	3e-05	HCN4, ABCC9, KCNH2, KCNJ2
regulation of membrane repolarization	3	121.5×	3e-05	AKAP9, KCNH2, KCNJ2
adult heart development	3	112.8×	4e-05	TCAP, MYH6, MYH7
regulation of cardiac muscle cell contraction	3	105.3×	5e-05	SCN5A, ANK2, KCNJ2
cardiac muscle hypertrophy in response to stress	3	98.7×	6e-05	TCAP, MYH6, MYH7
neurotrophin TRK receptor signaling pathway	3	98.7×	6e-05	SOS1, PTPN11, RAF1
regulation of cardiac muscle contraction	3	83.2×	1e-04	RYR2, HCN4, ANK2
skeletal muscle myosin thick filament assembly	2	351.1×	1e-04	TCAP, TTN
sarcomerogenesis	2	351.1×	1e-04	TCAP, TTN
membrane depolarization during Purkinje myocyte cell action potential	2	351.1×	1e-04	SCN5A, TRPM4

Therapeutics

Drugs indicated for this disease

0 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Adenosine	Phase 3 (in late-stage trials)
Amiodarone	Phase 3 (in late-stage trials)
Etripamil	Phase 3 (in late-stage trials)
Sotalol	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alcohol, Celivarone, Dantrolene, Epinephrine, Metoprolol.

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 12 · Phased (≥1): 13 · Undrugged: 21

Druggability breadth: 21 of 34 evidence-associated genes (62%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SCN5A	BEPRIDIL
SOS1	IDARUBICIN
CACNA1C	REMIFENTANIL
CACNB2	NIMODIPINE
MYLK2	FEDRATINIB
HCN4	IVABRADINE
ABCC9	PINACIDIL ANHYDROUS
KCNH2	CETIRIZINE
LMNA	BEPRIDIL
PRKAG2	ADENOSINE PHOSPHATE
PTPN11	ESTRAMUSTINE PHOSPHATE
RAF1	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMNA	823	4
KCNH2	706	4
SCN5A	108	4
CACNA1C	85	4
RAF1	31	4
MYLK2	19	4
PRKAG2	19	4
PTPN11	8	4
SOS1	5	4
ABCC9	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	CACNA1C, KCNH2, LMNA, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	LMNA, SCN5A
DIBUCAINE	4	CACNA1C, KCNH2, LMNA, SCN5A
IMIPRAMINE	4	CACNA1C, KCNH2, LMNA, SCN5A
DROPERIDOL	4	CACNA1C, KCNH2, LMNA, SCN5A
PONATINIB	4	KCNH2, SCN5A
DULOXETINE	4	CACNA1C, KCNH2, SCN5A
PALONOSETRON	4	KCNH2, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	LMNA, SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	CACNA1C, KCNH2, SCN5A
FEDRATINIB	4	KCNH2, MYLK2, SCN5A
QUINIDINE	4	CACNA1C, KCNH2, SCN5A
DARUNAVIR	4	KCNH2, SCN5A
DARIFENACIN	4	KCNH2, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	CACNA1C, KCNH2, LMNA, SCN5A
RANOLAZINE	4	KCNH2, SCN5A
PIMOZIDE	4	CACNA1C, KCNH2, LMNA, SCN5A
NIMODIPINE	4	CACNA1C, CACNB2, LMNA, SCN5A
FELODIPINE	4	LMNA, SCN5A
NICARDIPINE	4	CACNA1C, KCNH2, LMNA, SCN5A
AMLODIPINE	4	CACNA1C, KCNH2, SCN5A
PHENYTOIN	4	CACNA1C, KCNH2, SCN5A
PALIPERIDONE	4	KCNH2, SCN5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KCNH2	4,851	Binding:3558, Toxicity:1071, Functional:169, ADMET:53
RAF1	839	Binding:803, Functional:31, ADMET:5
SCN5A	594	Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1
PTPN11	588	Binding:585, Functional:2, ADMET:1
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
SOS1	421	Binding:409, Functional:12
PRKAG2	266	Binding:265, Functional:1
MYLK2	196	Binding:196
ABCC9	61	Functional:46, Binding:15
KCNJ2	31	Binding:23, ADMET:8
HCN4	30	Binding:20, ADMET:5, Functional:4, Toxicity:1
CACNB2	22	Binding:20, ADMET:1, Toxicity:1
RYR2	15	Binding:15
TRPM4	14	Binding:13, Functional:1
LMNA	12	Binding:9, Functional:3
VCL	2	Binding:2
DSP	2	Binding:2
TTN	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TTN	2.7.11.1	non-specific serine/threonine protein kinase
MYLK2	2.7.11.18	myosin-light-chain kinase
PTPN11	3.1.3.48	protein-tyrosine-phosphatase
RAF1	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SCN5A	594
SOS1	421
CACNA1C	575
MYLK2	196
KCNH2	4,851
PRKAG2	266
PTPN11	588
RAF1	839

Pharmacogenomics

Cohort genes with a PharmGKB record: 32; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

29 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	CACNA1C, KCNH2, LMNA, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	LMNA, SCN5A
DIBUCAINE	4	CACNA1C, KCNH2, LMNA, SCN5A
IMIPRAMINE	4	CACNA1C, KCNH2, LMNA, SCN5A
DROPERIDOL	4	CACNA1C, KCNH2, LMNA, SCN5A
PONATINIB	4	KCNH2, SCN5A
DULOXETINE	4	CACNA1C, KCNH2, SCN5A
PALONOSETRON	4	KCNH2, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	LMNA, SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	CACNA1C, KCNH2, SCN5A
FEDRATINIB	4	KCNH2, MYLK2, SCN5A
QUINIDINE	4	CACNA1C, KCNH2, SCN5A
DARUNAVIR	4	KCNH2, SCN5A
DARIFENACIN	4	KCNH2, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	CACNA1C, KCNH2, LMNA, SCN5A
PIMOZIDE	4	CACNA1C, KCNH2, LMNA, SCN5A
NIMODIPINE	4	CACNA1C, CACNB2, LMNA, SCN5A
FELODIPINE	4	LMNA, SCN5A
NICARDIPINE	4	CACNA1C, KCNH2, LMNA, SCN5A
AMLODIPINE	4	CACNA1C, KCNH2, SCN5A
PHENYTOIN	4	CACNA1C, KCNH2, SCN5A
PALIPERIDONE	4	KCNH2, SCN5A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	SCN5A, SOS1, CACNA1C, CACNB2, MYLK2, HCN4, ABCC9, KCNH2, LMNA, PRKAG2 (+2 more)
B	Phased (≥1) drug, not yet approved	1	RYR2
C	Druggable family + PDB, no drug	4	TTN, TRPM4, DPP6, KCNJ2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	17	SNTA1, TCAP, VCL, LDB3, RBM20, DSP, DTNA, EYA4, FKTN, AKAP9 (+7 more)

Undrugged target profiles

21 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SNTA1	0	SCN5A
RBM20	0	ABCC9
DPP6	0	SCN5A
EYA4	0	ABCC9
PKP2	0	SCN5A
TCAP	0	—
TTN	1	—
VCL	2	—
LDB3	0	—
TRPM4	14	—
DSP	2	—
DTNA	0	—
FKTN	0	—
AKAP9	0	—
TTN-AS1	0	—
ANK2	0	—
ITFG2-AS1	0	—
KCNJ2	31	—
LAMA4	0	—
MYH6	0	—
MYH7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 283.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	241
PHASE4	18
PHASE3	9
PHASE2	4
EARLY_PHASE1	4
PHASE1/PHASE2	3
PHASE1	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03833089	PHASE4	ACTIVE_NOT_RECRUITING	Targeted Potassium Levels for Prevention of ICD Therapy
NCT00257959	PHASE4	COMPLETED	Optimal Pharmacological Therapy In Implantable Defibrillator Patients (OPTIC)
NCT00383799	PHASE4	TERMINATED	Iv Amiodarone Versus Iv Procainamide to Treat Haemodynamically Well Tolerated Ventricular Tachycardia
NCT00401466	PHASE4	COMPLETED	Remote Follow-up of Patients Receiving Implantable Cardioverter Defibrillator for Prophylactic Therapy
NCT00412607	PHASE4	COMPLETED	Catheter Evaluation for Endocardial Ablation in Patients With Ventricular Tachycardia
NCT00538356	PHASE4	COMPLETED	Influence of Home Monitoring on the Clinical Status of Heart Failure Patients With an Impaired Left Ventricular Function
NCT00787800	PHASE4	COMPLETED	The Use of Dual Chamber ICD With Special Programmed Features to Lower the Risk of Inappropriate Shock
NCT00851279	PHASE4	COMPLETED	Stereotaxis Study To Obliterate Persistent Ventricular Tachycardia
NCT00905853	PHASE4	COMPLETED	Ventricular Tachycardia (VT) Ablation or Escalated Drug Therapy
NCT01557842	PHASE4	TERMINATED	Early Ablation Therapy for the Treatment of Ischemic Ventricular Tachycardia in Patients With Implantable Cardioverter Defibrillators
NCT01558830	PHASE4	UNKNOWN	Safety of Amiodarone and Ranolazine Together in Patients With Angina
NCT01780311	PHASE4	UNKNOWN	Catheter Ablation Versus Antiarrhythmic Drugs for Outflow Tract Ventricular ARrhythmias
NCT02083016	PHASE4	COMPLETED	Ultra-high Density Mapping With Multielectrode Catheter vs Conventional Point by Point Mapping for Ventricular Tachycardia Substrate Ablation
NCT02114528	PHASE4	TERMINATED	Anti-arrhythmic Therapy vs Catheter Ablation as First Line Treatment for AICD Shock Prevention
NCT02666742	PHASE4	COMPLETED	DOACs for Stroke Prevention Post Ventricular Tachycardia Ablation
NCT02830360	PHASE4	COMPLETED	Antiarrhythmics or Ablation for Ventricular Tachycardia 2
NCT03855826	PHASE4	UNKNOWN	Evaluation of the Efficacy and Safety of Nifekalant Hydrochloride (NIF) Injection.
NCT04694079	PHASE4	COMPLETED	Ventricular Tachycardia Ablation and Myocardial Scar Characterization With Magnetic Resonance
NCT05047198	PHASE3	RECRUITING	Catheter Ablation Versus Radio-Ablation for Ventricular Tachycardia: a Randomized Controlled Trial
NCT06281977	PHASE3	RECRUITING	Study Evaluating Dexmedetomidine in the Acute Treatment of Electrical Storm
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01038960	PHASE3	COMPLETED	Exercise Training in ICD Recipients; Effect on Therapy Delivered, Depression and Anxiety
NCT01045668	PHASE3	COMPLETED	Ablation of Clinical Ventricular Tachycardia Versus Addition of Substrate Ablation on the Long Term Success Rate of VT Ablation
NCT01798277	PHASE3	WITHDRAWN	Trial Comparing Ablation With Medical Therapy in Patients With Ventricular Tachycardia
NCT01898221	PHASE3	COMPLETED	Vein of Marshall Ethanol Infusion for Persistent Atrial Fibrillation
NCT04134845	PHASE2/PHASE3	COMPLETED	A Clinical Trial Utilizing Dantrolene in Patients With Ventricular Arrhythmias.
NCT04675073	PHASE3	UNKNOWN	Preventive VT Substrate Ablation in Ischemic Heart Disease
NCT05078684	PHASE3	UNKNOWN	GANGlion Stellate Block for Treatment of Electric storRm (GANGSTER Trial)
NCT04984265	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	SBRT in Chagas Disease Ventricular Tachycardia
NCT05258422	PHASE2	ENROLLING_BY_INVITATION	Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia (StAR-VT)
NCT05439031	PHASE2	RECRUITING	StereoTactic Arrhythmia Radiotherapy in the NetherLands no. 2
NCT05511246	PHASE2	RECRUITING	Venous Ethanol for Ventricular Tachycardia
NCT00534300	PHASE1/PHASE2	COMPLETED	Intravenous n-3 Fatty Acids and Ventricular Tachycardia in Patients With Implantable Cardioverter Defibrillator (ICD)-Pacemaker
NCT02919618	PHASE1/PHASE2	COMPLETED	Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
NCT06005428	PHASE2	TERMINATED	Effectiveness of CRD-4730 in Participants With Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
NCT05594368	PHASE1	RECRUITING	Dose Escalation for SBRT of Recurrent VT Ventricular Tachyarrhythmia - a Single Center, Phase II Clinical Trial
NCT02003001	PHASE1	UNKNOWN	Botulinum Toxin Injection to Prevent Ventricular Arrhythmias
NCT04770051	PHASE1	WITHDRAWN	Percutaneous Inferior Cervical Sympathetic Block for Treatment of Refractory Ventricular Tachycardia
NCT05377216	EARLY_PHASE1	RECRUITING	Characterization of Cardiac Electrophysiological Effects of Autonomic Neuromodulation
NCT02891863	EARLY_PHASE1	TERMINATED	Low Energy Therapy to Convert Ventricular Tachycardias

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AMIODARONE	4	9
ALCOHOL	4	2
DANTROLENE	4	2
RANOLAZINE	4	2
SOTALOL	4	2
ADENOSINE	4	1
ASPIRIN	4	1
FISH OIL TRIGLYCERIDES	4	1
MIDAZOLAM HYDROCHLORIDE	4	1
NIFEKALANT	3	2
IOBENGUANE I 123	1	1
CHEMBL606298	0	1
CHEMBL454299	0	1